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Effect of intestinal lymphatic circulation blockage in two-hit rats 被引量:29
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作者 Chun-Yu Niu Ji-Cheng Li +2 位作者 Zi-Gang Zhao Jing Zhang Xue-Hui Shao 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第36期5805-5812,共8页
AIM: To study the effect of blocking intestinal lymphatic circulation in two-hit rats and explore the significance of intestinal lymphatic circulation in two-hit. METHODS: Wistar rats were divided equally into three g... AIM: To study the effect of blocking intestinal lymphatic circulation in two-hit rats and explore the significance of intestinal lymphatic circulation in two-hit. METHODS: Wistar rats were divided equally into three groups: mesenteric lymph duct ligation group, non- ligation group and sham group. Mesenteric lymph was diverted by ligation of mesenteric lymph duct, and the two-hit model was established by hemorrhage and lipopolysaccharide (LPS) methods. All rats were sampled for serum pre-experiment and 24 h post- experiment. The organs including kidney, liver, lung and heart were collected for pathomorphologic observation and biochemical investigation. The nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) were determined in serum and tissue homogenate. RESULTS: Pathomorphology study showed that the structures of kidney, lung, liver and heart tissues were normal in sham group; congestion, degeneration and necrosis in non-ligation group; but only mild lesions in ligation group. After two-hits, the contents of AST, ALT, BUN, Cr and LDH-1 in the serum of non-ligation group and ligation group were obviously higher than that in pre-experiment group and sham group, but obviously lower than that in non-ligation group. The contents of NO2-/NO3-, NOS, iNOS and MDA in the serum of non- ligation group were significantly increased, compared with pre-experiment and sham group, but SOD was significantly lower. These parameters were significantly different in ligation group compared with that in sham group, but NO2-/NO3-, iNOS and MDA in ligation group were significantly lower than that in non-ligation group. CONCLUSION: Ligation of mesenteric lymph duct could improve the disturbance of organic function and morphologic damage in two-hit rats; the lymphatic mechanism in two-hit should be emphasized. 展开更多
关键词 two-hit Mesenteric lymph duct LIGATION ORGANS Humoral factor
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“二次打击”脓毒症继发肺炎大鼠模型的构建与评价 被引量:4
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作者 陈颖颖 李慧贤 +3 位作者 马帅 邓博 卢建新 丁峰 《中华危重病急救医学》 CAS CSCD 北大核心 2015年第10期805-810,共6页
目的:模拟临床脓毒症继发感染的发病情况,构建“二次打击”动物模型,评价“二次打击”对机体损害及免疫功能的影响。方法81只雄性SD大鼠按随机数字表法分组,其中45只分为单纯脓毒症组及脓毒症继发肺炎4 d、7 d组,每组15只,用于观... 目的:模拟临床脓毒症继发感染的发病情况,构建“二次打击”动物模型,评价“二次打击”对机体损害及免疫功能的影响。方法81只雄性SD大鼠按随机数字表法分组,其中45只分为单纯脓毒症组及脓毒症继发肺炎4 d、7 d组,每组15只,用于观察生存情况;另外36只分为正常对照组,单纯脓毒症1、4、7 d组,脓毒症继发肺炎4 d、7 d组,每组6只,用于指标检测。采用盲肠结扎穿孔术(CLP)建立脓毒症模型;于CLP术后4 d或7 d分别经鼻腔注射肺炎链球菌(含菌量1×1010 cfu/mL)继发肺部感染构建“二次打击”模型。分别于相应时间点以及给菌后1 d处死大鼠,收集血液及脾脏组织,进行外周血菌落计数、脾脏细胞计数,检测血清生化指标及相关细胞因子水平,观察脾脏病理改变及细胞凋亡情况。结果①与单纯脓毒症组同期比较,脓毒症继发肺炎4 d组大鼠存活数明显减少(只:4比11,χ2=6.533,P=0.011),而7 d组则差异无统计学意义(只:9比11,χ2=0.600,P=0.439)。②单纯脓毒症组术后1 d外周血菌落计数、生化指标均明显升高,随后逐渐下降;术后4 d时脾脏免疫细胞计数已明显低于1 d〔树突细胞(DC):(0.69±0.09)%比(0.87±0.31)%, CD4+ T细胞:(21.05±2.89)%比(24.84±4.59)%,CD8+ T细胞:(10.62±1.79)%比(13.40±1.31)%,均P<0.05〕,而调节性T细胞(Treg)明显高于正常对照组〔(3.14±0.74)%比(2.87±1.08)%,P<0.05〕;术后7 d血生化指标丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、尿素氮(BUN)、血肌酐(SCr)较1 d明显下降〔ALT(U/L):35.33±11.52比81.00±38.40,AST(U/L):70.33±42.16比156.00±28.11,BUN(mmol/L):5.30±2.27比9.13±4.04,SCr(μmol/L):55.33±10.67比96.67±45.79,均P<0.05〕;血清促炎因子肿瘤坏死因子-α(TNF-α)、白细胞介素(IL-6、IL-1β)高峰出现在术后1 d〔TNF-α为(18.03±2.88)ng/L,IL-6为(10.37±4.20)ng/L,IL-1β为(102.44±51.46)ng/L〕,高迁移率族蛋白B1(HMGB1)高峰出现在术后4 d〔(1.76±0.71)μg/L〕;抗炎因子转化生长因子-β1(TGF-β1)和可溶性肿瘤坏死因子受体-Ⅰ(sTNFR-Ⅰ)于脓毒症后期仍维持在较高水平〔术后7 d TGF-β1为(0.90±0.56)ng/L,sTNFR-Ⅰ为(1.56±0.39) ng/L〕。苏木素-伊红(HE)染色显示,单纯脓毒症组CLP术后脾脏组织病理改变随时间延长逐渐加重,术后4 d脾脏凋亡细胞数明显高于术后1 d(个/HP:52.99±20.79比16.05±3.28,P<0.05)。③与单纯脓毒症组同期比较,脓毒症继发肺炎4 d组外周血菌落数明显增多(log cfu/mL:1.78±0.54比0.25±0.18,P<0.05),而7 d组则差异无统计学意义(log cfu/mL:0.57±0.46比0.13±0.12,P>0.05)。脓毒症继发肺炎4 d、7 d组各脾脏免疫细胞计数及生化指标变化趋势与单纯脓毒症组相似,虽较单纯脓毒症组同期有所减少,但差异均无统计学意义。与单纯脓毒症组同期比较,脓毒症继发肺炎4 d组HMGB1进一步减少(μg/L:1.17±0.74比1.76±0.71,P<0.05),脓毒症继发肺炎7 d组IL-1β进一步升高(ng/L:105.73±25.06比61.04±31.29,P<0.05),其余炎症因子水平则差异无统计学意义。脓毒症继发肺炎4 d组脾脏凋亡细胞较单纯脓毒症组同期明显增加(个/HP:74.48±22.47比52.99±20.79,P<0.05),而7 d组则差异无统计学意义(个/HP:28.70±4.13比30.43±14.55, P>0.05)。结论 CLP术后4 d继发肺炎“二次打击”模型较单纯CLP致脓毒症模型死亡大鼠明显增加,细菌清除力下降,免疫细胞数量减少且凋亡加重,这可能与病程中期机体存在的免疫麻痹有关。CLP术后7 d继发肺炎“二次打击”模型表现为宿主免疫功能重构,可能与免疫应答能力逐渐恢复有关。 展开更多
关键词 脓毒症 动物模型 “二次打击” 免疫麻痹 "two-hit"
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